Emerging Infectious Diseases

The pandemic of COVID-19 disease, a respiratory condition caused by a novel coronavirus (SARS-CoV-2) in December 2019, has been evidently effectively controlled by vaccines. As of 31st May 2021, there are 170,189,835 confirmed cases in over 240 countries with over 3,538,196 deaths. It is characterized by a myriad of both respiratory and non-respiratory symptoms. Most individuals with the infection will have mild symptoms that are naturally resolved by an active immune system. However, a subset of people with a higher risk of infection is the elderly and those with comorbidities such as heart disease, diabetes, asthma, and cancer. The human immune response against viral infection is mainly dependent on active T cell function. Glutathione (GSH), a ubiquitous tri-peptide antioxidant known for homeostasis regulation and important in oxidative stress response, is essential for T cell effector functions through its regulation of metabolic activity.

Glutamyl cysteine ligase (GCL) catalyses the rate-limiting step of glutathione synthesis. Polymorphisms in this enzyme impede glutathione synthesis. Glutathione S‐transferases (GSTs) catalyse the conjugation of glutathione to xenobiotic, reactive oxygen species (ROS), toxins, and other cellular by products. Alterations in the structure, function, or level of expression of GST genes could alter the ability of the cell to inactivate toxins, thereby aggravating the progression of infection. GST polymorphisms have been clearly associated with such comorbidities including various cancers and respiratory diseases. It is well known that oxidative stress is a major factor in the pathogenesis of viral respiratory infections. Evidently, full dosed individual is still susceptible to infection and severe illness from the virus with possible hospitalization. Recovery from infection is associated with traumatic pain and fatigue, breathlessness, and negatively impacted morbidity. It is therefore possible that GST polymorphisms may impair immune response against the coronavirus. To the best of our knowledge, the potential implications of GCLC & GST gene polymorphisms on SARS-CoV-2 infection have not been elucidated.